Biocompatible polymeric coating containing therapeutic agents

Abstract

A method of preparing a biocompatible polymeric coating includes preparing an aqueous polymer solution by contacting and reacting methacrylic acid and at least one methacrylate or phosphorylcholine. The methacrylate or phosphorylcholine may include hydroxyethyl methacrylate, polyethylene glycol monomethacrylate, or methacryloyloxyethyl phosphorylcholine. An aqueous coupling agent solution is prepared and is either applied to the substrate surface or is mixed with the polymer solution to form a coating solution. If the coupling agent solution was first applied to the substrate surface, the polymer solution is then applied to the primed substrate surface. Alternatively if a coating solution was created, the coating solution is applied to the substrate surface. In either event, the polymer solution and coupling agent solution react with the substrate to form the biocompatible polymeric coating on the substrate surface.

What is claimed is: 
     
       1. A method of preparing a biocompatible polymeric coating comprising:
 a) preparing an aqueous polymer solution by contacting and reacting:
 i) methacrylic acid (MAA), 
 ii) methacryloyloxyethyl phosphorylcholine (MPC), and 
 iii) at least one methacrylate selected from the list consisting of hydroxyethyl methacrylate (HEMA), poly(ethylene glycol) monomethacrylate (PEGMA), and poly(ethylene glycol) methyl ether methacrylate (MAPEG), wherein a weight percent of MPC is at least 60%; 
 
 b) precipitating a reaction product within the aqueous polymer solution by addition of acetone to produce a clear solid polymer material; 
 c) dissolving the clear solid polymer material in an alcohol or water to produce a purified polymer solution; 
 d) preparing an aqueous polyaziridine coupling agent solution; and 
 e) mixing the purified polymer solution with the coupling agent solution to form the biocompatible polymeric coating. 
 
     
     
       2. A method of applying a biocompatible polymeric coating to a substrate surface, the method comprising:
 A) preparing the biocompatible polymeric coating in accordance with  claim 1 ; and 
 B) contacting and reacting the coating solution with the substrate surface to coat the surface with the biocompatible polymeric coating. 
 
     
     
       3. The method of  claim 2  further comprises:
 C) loading the polymer solution in a first syringe prior to the mixing step; and 
 D) loading the coupling agent solution in a second syringe prior to the mixing step, 
 wherein the mixing step includes dispensing a first volume of polymer solution from the first syringe and dispensing a second volume of coupling agent solution from the second syringe. 
 
     
     
       4. The method of  claim 3  wherein the first syringe and the second syringe comprise a dual cartridge syringe. 
     
     
       5. The method of  claim 3  wherein the first volume is the same as the second volume. 
     
     
       6. The method of  claim 2  wherein a therapeutic agent solution is further added during at least one of steps A) and B). 
     
     
       7. The method of  claim 2  further comprising:
 C) pretreating the substrate surface to functionalize the substrate surface for reactivity with aqueous coupling agent solution and/or coating solution, wherein step C) occurs prior to step B). 
 
     
     
       8. A method of applying a biocompatible polymeric coating to a substrate surface, the method comprising:
 a) preparing an aqueous polymer solution by contacting and reacting:
 i) methacrylic acid (MAA), 
 ii) methacryloyloxyethyl phosphorylcholine (MPC), and 
 ii) at least one methacrylate selected from the list consisting of hydroxyethyl methacrylate (HEMA), poly(ethylene glycol) monomethacrylate (PEGMA), and poly(ethylene glycol) methyl ether methacrylate (MAPEG), wherein a weight percent of MPC is at least 60%; 
 
 b) precipitating a reaction product within the aqueous polymer solution by addition of acetone to produce a clear solid polymer material; 
 c) dissolving the clear solid polymer material in an alcohol or water to produce a purified polymer solution; 
 d) preparing an aqueous polyaziridine coupling agent solution; 
 e) contacting and reacting the aqueous coupling agent solution with the substrate surface to form a primed substrate surface; and 
 f) contacting and reacting the aqueous polymer solution with the primed substrate surface to coat the surface with the biocompatible polymeric coating. 
 
     
     
       9. The method of  claim 8  further comprising:
 g) pretreating the substrate surface to functionalize the substrate surface for reactivity with the aqueous coupling agent solution, wherein step g) occurs prior to step e).